There is evidence that insulin-dependent diabetes mellitus (IDDM) is a chronic autoimmune disease in which the presence of autoantibodies such as cytoplasmic islet cell antibodies (ICA), anti-glutamic acid decarboxylase (GAD) autoantibodies and anti-insulin autoantibodies are found years before the clinical onset of the disease (Eisenbarth, G. S. (1986) N. Engl. J. Med. 314:1360-1368). A common feature of Type I diabetes and other autoimmune diseases is a humoral immune response that can be manifested by the appearance of autoantibodies against cellular proteins (Tan, E. M. (1991) Cell :841-842). To date, only a few autoantigens associated with Type I diabetes mellitus have been identified, namely insulin (Palmer, J. P. et al (1983) Science 222:1337-1339), GAD (Baekkeskov, S. et al. (1990) Nature 347:151-156) and carboxypeptidase H (Castano, L. et al. (1991) J. Clin. Endocr. Metab. 73:1197-1201), and the glycolipids GT3 (Gillard, B. K., et al. (1989) Journal Immunol. Methods 142:3826-3832) and GM2-1 (Dotta, F., et al. (1992) Endocrinology 130:37-42).
Recently cDNA encoding a fragment of carboxypeptidase H, a granule-associated enzyme, has been reported to react with sera from prediabetic patients (Gillard, B. K., et al, supra) and another protein expressed in a λgtll phage from a human islet library appear to be recognized by IDDM sera (Rabin, D. U., et al. (1992) Diabetes 11:183-186). Cellular proteins of unknown sequence whose molecular weights are 38 kD (Roep, B. O., et al. (1991) Lancet 337:1439-1441), 52 kD (Karounos, D. G., and J. W. Thomas (1990) Diabetes 89:1085-1090), and 69 kD (Martin, J. M., et al. (1991) Ann. Med, 23:447-452), have also been reported to be recognized by a humoral and/or a cellular immune response. It is of interest that almost all patients with Type I diabetes have elevated levels of IgG anti-bovine serum albumin (BSA) antibodies which precipitate a Mr 69,000 islet peptide which may represent a target antigen for cow milk induced islet autoimmunity (Martin, J. M., et al., supra; and Dosh, H-M, et al. (1991) Pediatr. Adolesc. Endocrinol. 21:). The identification of additional antigens associated with the development of diabetes could improve the ability of clinicians to evaluate the risk of development of the disease.